title: Dimeric cinnamoylamide derivatives as inhibitors of melanogenesis.
abstract: Dimeric cinnamoylamide derivatives were synthetized and tested as inhibitors of tyrosinase activity and melanin formation. The most active dimeric cinnamoylamide derivatives was dimeric compound of p-coumaric acid (compound 1) that inhibited tyrosinase activity more efficiently than p-coumaric acid. It also inhibited melanin production by B16 melanoma cell line and normal human melanocytes more efficiently than kojic acid. We next investigated the potential mutagenic and skin sensitization effect of compound 1. Compound 1 was found to induce no mutagenic activity, no irritation and no delayed contact hypersensitivity at the maximum concentration of 10%. In vitro percutaneous absorption studies exhibited that compound 1 could diffuse across the skin till its site of action. All these results lead us to propose that compound 1 may be a safe and effective candidate for treating skin hyperpigmentation related disorders.
authors.affiliation: Mayoly Spindler Laboratory, Preclinical R&D, Chatou Cedex, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Criton
authors.forename: Véronique
authors.initials: V
authors.lastname: Le Mellay-Hamon
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D003373:Coumaric Acids / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D003879:Dermatologic Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D019281:Dimerization; D005029:Ethylenediamines / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D017495:Hyperpigmentation / Q000188:drug therapy* / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D011753:Pyrones / Q000494:pharmacology; D012869:Skin Absorption; D012871:Skin Diseases / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D003373:Coumaric Acids; D003879:Dermatologic Agents; D005029:Ethylenediamines; D008543:Melanins; D011753:Pyrones; C011890:kojic acid; D014442:Monophenol Monooxygenase